ArticleEuropean journal of pharmacology2014
Targeting putative mu opioid/metabotropic glutamate receptor-5 heteromers produces potent antinociception in a chronic murine bone cancer model.
Article in European journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Targeting Excitatory Glutamate Receptors for Morphine Tolerance: A Narrative Review.CNS neuroscience & therapeutics · 2025Review
- MMG22 Potently Blocks Hyperalgesia in Cisplatin-treated Mice.Neuroscience · 2023Article
- Analgesic efficacy of sleep-promoting pharmacotherapy in patients with chronic pain: a systematic review and meta-analysis.Pain reports · 2023Review
- Contributions of the International Narcotics Research Conference to Opioid Research Over the Past 50 years.Advances in drug and alcohol research · 2022Review
- GPCR heteromers: An overview of their classification, function and physiological relevance.Frontiers in endocrinology · 2022Review
- Intrathecal administration of Resolvin D1 and E1 decreases hyperalgesia in mice with bone cancer pain: Involvement of endocannabinoid signaling.Prostaglandins & other lipid mediators · 2020Article
- Article
- Activation of µ-δ opioid receptor heteromers inhibits neuropathic pain behavior in rodents.Pain · 2020Article
- Targeting MOR-mGluRNeuropharmacology · 2019Article
- The bivalent ligand MCC22 potently attenuates hyperalgesia in a mouse model of cisplatin-evoked neuropathic pain without tolerance or reward.Neuropharmacology · 2019Article
- Developing a Biased Unmatched Bivalent Ligand (BUmBL) Design Strategy to Target the GPCR Homodimer Allosteric Signaling (cAMP over β-Arrestin 2 Recruitment) Within the Melanocortin Receptors.Journal of medicinal chemistry · 2019Article
- Bivalent ligand MCC22 potently attenuates nociception in a murine model of sickle cell disease.Pain · 2018Article
- Article
- Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics.Anesthesia and analgesia · 2017Review
- A Direct in Vivo Comparison of the Melanocortin Monovalent Agonist Ac-His-DPhe-Arg-Trp-NHACS chemical neuroscience · 2017Article
- Current and Future Issues in the Development of Spinal Agents for the Management of Pain.Current neuropharmacology · 2017Review
- Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction.The international journal of neuropsychopharmacology · 2016Article
- An in Vitro and in Vivo Investigation of Bivalent Ligands That Display Preferential Binding and Functional Activity for Different Melanocortin Receptor Homodimers.Journal of medicinal chemistry · 2016Article
- Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes.Neural plasticity · 2016Review
- Basic Pharmacological and Structural Evidence for Class A G-Protein-Coupled Receptor Heteromerization.Frontiers in pharmacology · 2016Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The therapeutic management of chronic pain associated with many cancers is problematic due to the development of tolerance and other adverse effects during the disease progression. Recently we reported on a bivalent ligand (MMG22) containing both mu agonist and mGluR5 antagonist pharmacophores that produced potent antinociception in mice with LPS-induced acute inflammatory pain via a putative MOR-mGluR5 heteromer. In the present study we have investigated the antinociception of MMG22 in a mouse model of bone cancer pain to determine its effectiveness in reducing this type of chronic nociception. There was a 572-fold increase in the potency of MMG22 over a period of 3-21 days that correlated with the progressive increase in hyperalgesia induced by bone tumor growth following implantation of fibrosarcoma cells in mice. The enhancement of antinociception with the progression of the cancer is possibly due to inhibition of NMDA receptor-mediated hyperalgesia via antagonism of mGluR5 and concomitant activation of MOR by the MMG22-occupied heteromer. Notably, MMG22 was 3.6-million-fold more potent than morphine at PID 21. Since MMG22 exhibited a 250,000-times greater potency than that of a mixture of the mu opioid (M19) agonist and mGluR5 antagonist (MG20) monovalent ligands, the data suggest that targeting the putative MOR-mGluR5 heteromer is far superior to univalent interaction with receptors in reducing tumor-induced nociception. In view of the high potency, long duration (>24h) of action and minimal side effects, MMG22 has the potential to be a superior pharmacological agent than morphine and other opiates in the treatment of chronic cancer pain and to serve as a novel pharmacologic tool.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.